Collaborative Management of HIV Infection in the Community: An Effort to Improve the Quality of HIV Care

Our hospital led a multidisciplinary community team to improve the quality of care delivered to HIV-infected clients utilizing a disease management approach in a US metropolitan community of 150,000 people. Community needs assessment and client and community surveys were used to define the problems. Patient care flowcharting and the creation of an electronic patient database facilitated patient tracking across the entire community. Clinical guidelines and a consultation and referral immunology clinic standardized care practices. Measurable improvements in the quality of care were noted in multiple areas. Flowchart completion rates rose from 44% to 100%; medication adherence assessment rose from 82% to 100%; immunization rates rose from a mean of 72% to a mean of 87%; PPD screening rose from a low of 35% to a high of 87%; perinatal transmission rates fell from 31% to 4%; and Emergency Department utilization decreased. Two essential components of the effort were the establishment of a full-time leadership position in the form of a clinical nurse practitioner and the creation of an electronic database with flowcharting to standardize the measurement, delivery and tracking of care. The programme has become an example of successful disease management through hospital-community collaboration

Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP) syndrome

Adenopathy and extensive skin patch overlying a plasmacytoma is a very rare syndrome featuring a red-to-brown, violaceous skin patch along with a plasmacytoma. Only 11 case reports exist in the literature. Skin biopsies from the cutaneous patch overlying the plasmacytoma exhibit a dermal vascular hyperplasia with increased surrounding dermal mucin. Radiation therapy is used to treat and cure the plasmacytoma

A protocol for investigation of the effects of outdoor air pollution on stroke incidence, phenotypes and survival using the South London Stroke Register.

Stroke is a major cause of death and disability. About 5.3 million people die every year from stroke worldwide with over 9 million people surviving at any one time after suffering a stroke. About 1 in 4 men and 1 in 5 women aged 45 years will suffer a stroke if they live to their 85th year. It is estimated that by 2023 there will be an absolute increase in the number of people experiencing a first ever stroke of about 30% compared with 1983. In the UK, stroke is the third commonest cause of death and the most common cause of adult physical disability and consumes 5% of the health and social services budget. Stroke is assuming strategic public health importance because of increased awareness in society, an ageing population and emerging new treatments. It is an NHS health service and research priority, being identified as a target in Our Healthier Nation and the NSF for Older People for prevention and risk factor control and in the NHS Plan as a disease requiring intermediate care planning and reduction in inequalities of care. Whilst a number of risk factors for stroke are well known (e.g. increasing age, ethnicity, socioeconomic deprivation, hypertension), the potential importance of outdoor air pollution as a modifiable risk factor is much less well recognised. This is because studies to date are inconclusive or have methodological limitations. In Sheffield, we estimated that 11% of stroke deaths may be linked to current levels of outdoor air pollution and this high figure is explained by the fact that so many people are exposed to air pollution.We plan to study the effects of outdoor air pollution on stroke using a series of epidemiological (i.e. population based) studies. The purpose of this project is: to examine if short term increases in pollution can trigger a stroke in susceptible individuals, to investigate if the occurrence of stroke is higher amongst people living in more polluted areas (which would be explained by a combination of exposure to short term increases and longer term exposure to higher pollution levels), and to see if people living in more polluted areas have reduced survival following their stroke. We will use geographical information systems, robust statistical methods and powerful grid computing facilities to link and analyse the data. The datasets we will use are the South London Stroke Register database, daily monitored pollution data from national monitoring networks and modelled pollution data for London from the Greater London Authority. The South London Stroke Register records information on all patients who suffer a stroke ("incident" cases) living within a defined area. This stroke incidence dataset offers major advantages over previous studies examining the effects of pollution on hospital admissions and mortality, as not all patients with stroke are admitted or die and there may be a delay between the onset of stroke and admission or death. In addition, it contains other useful information, particularly the type of stroke people have suffered. Air pollution is a potentially modifiable risk factor for stroke. This study will provide robust population level evidence regarding the effects of outdoor air pollution on stroke. If it confirms the link, it will suggest to policy-makers at national and international levels that targeting policy interventions at high pollution areas may be a feasible option for stroke prevention

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

An Unusual Transmission Spectrum for the Sub-Saturn KELT-11b Suggestive of a Sub-Solar Water Abundance

We present an optical-to-infrared transmission spectrum of the inflated sub-Saturn KELT-11b measured with the Transiting Exoplanet Survey Satellite (TESS), the Hubble Space Telescope (HST) Wide Field Camera 3 G141 spectroscopic grism, and the Spitzer Space Telescope (Spitzer) at 3.6 $\mu$m, in addition to a Spitzer 4.5 $\mu$m secondary eclipse. The precise HST transmission spectrum notably reveals a low-amplitude water feature with an unusual shape. Based on free retrieval analyses with varying molecular abundances, we find strong evidence for water absorption. Depending on model assumptions, we also find tentative evidence for other absorbers (HCN, TiO, and AlO). The retrieved water abundance is generally $\lesssim 0.1\times$ solar (0.001--0.7$\times$ solar over a range of model assumptions), several orders of magnitude lower than expected from planet formation models based on the solar system metallicity trend. We also consider chemical equilibrium and self-consistent 1D radiative-convective equilibrium model fits and find they too prefer low metallicities ($[M/H] \lesssim -2$, consistent with the free retrieval results). However, all the retrievals should be interpreted with some caution since they either require additional absorbers that are far out of chemical equilibrium to explain the shape of the spectrum or are simply poor fits to the data. Finally, we find the Spitzer secondary eclipse is indicative of full heat redistribution from KELT-11b's dayside to nightside, assuming a clear dayside. These potentially unusual results for KELT-11b's composition are suggestive of new challenges on the horizon for atmosphere and formation models in the face of increasingly precise measurements of exoplanet spectra.Comment: Accepted to The Astronomical Journal. 31 pages, 20 figures, 7 table

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

T. gondii RP Promoters & Knockdown Reveal Molecular Pathways Associated with Proliferation and Cell-Cycle Arrest

Molecular pathways regulating rapid proliferation and persistence are fundamental for pathogens but are not elucidated fully in Toxoplasma gondii. Promoters of T. gondii ribosomal proteins (RPs) were analyzed by EMSAs and ChIP. One RP promoter domain, known to bind an Apetela 2, bound to nuclear extract proteins. Promoter domains appeared to associate with histone acetyl transferases. To study effects of a RP gene's regulation in T. gondii, mutant parasites (Δrps13) were engineered with integration of tetracycline repressor (TetR) response elements in a critical location in the rps13 promoter and transfection of a yellow fluorescent-tetracycline repressor (YFP-TetR). This permitted conditional knockdown of rps13 expression in a tightly regulated manner. Δrps13 parasites were studied in the presence (+ATc) or absence of anhydrotetracycline (-ATc) in culture. -ATc, transcription of the rps13 gene and expression of RPS13 protein were markedly diminished, with concomitant cessation of parasite replication. Study of Δrps13 expressing Myc-tagged RPL22, -ATc, showed RPL22 diminished but at a slower rate. Quantitation of RNA showed diminution of 18S RNA. Depletion of RPS13 caused arrest of parasites in the G1 cell cycle phase, thereby stopping parasite proliferation. Transcriptional differences ±ATc implicate molecules likely to function in regulation of these processes. In vitro, -ATc, Δrps13 persists for months and the proliferation phenotype can be rescued with ATc. In vivo, however, Δrps13 could only be rescued when ATc was given simultaneously and not at any time after 1 week, even when L-NAME and ATc were administered. Immunization with Δrps13 parasites protects mice completely against subsequent challenge with wildtype clonal Type 1 parasites, and robustly protects mice against wildtype clonal Type 2 parasites. Our results demonstrate that G1 arrest by ribosomal protein depletion is associated with persistence of T. gondii in a model system in vitro and immunization with Δrps13 protects mice against subsequent challenge with wildtype parasites

Negative emotional stimuli reduce contextual cueing but not response times in inefficient search

In visual search, previous work has shown that negative stimuli narrow the focus of attention and speed reaction times (RTs). This paper investigates these two effects by first asking whether negative emotional stimuli narrow the focus of attention to reduce the learning of a display context in a contextual cueing task and, second, whether exposure to negative stimuli also reduces RTs in inefficient search tasks. In Experiment 1, participants viewed either negative or neutral images (faces or scenes) prior to a contextual cueing task. In a typical contextual cueing experiment, RTs are reduced if displays are repeated across the experiment compared with novel displays that are not repeated. The results showed that a smaller contextual cueing effect was obtained after participants viewed negative stimuli than when they viewed neutral stimuli. However, in contrast to previous work, overall search RTs were not faster after viewing negative stimuli (Experiments 2 to 4). The findings are discussed in terms of the impact of emotional content on visual processing and the ability to use scene context to help facilitate search

National Athletic Trainers' Association Position Statement: Management of Sport Concussion

To provide athletic trainers, physicians, and other health care professionals with best-practice guidelines for the management of sport-related concussions