Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses

Cancer symptom awareness and barriers to symptomatic presentation in England – Are we clear on cancer?

Background: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. Methods: Using a uniquely large data set (n=49?270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. Results: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor’s surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. Conclusions: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes

Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat

Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10-08). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution

Self-Collected Mid-Turbinate Swabs for the Detection of Respiratory Viruses in Adults with Acute Respiratory Illnesses

BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and followed up for symptoms of influenza. They were asked to have NP and MT swabs taken as soon as possible after the onset of a fever or two or more respiratory symptoms with an acute onset. The swabs were tested for viral respiratory infections using Seeplex® RV12 multiplex PCR detection kit. Seventy six pairs of simultaneous NP and MT swabs were collected from 38 symptomatic subjects. Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both. Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS: Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses. Given the ease of MT collection and similar results between the two swabs, it is likely that MT swabs should be the preferred method of respiratory cell collection for outpatient studies. In light of this data, larger studies should be performed to ensure that this still holds true and data should also be collected on the patient preference of collection methods

Cluster-randomized trial of a web-assisted tobacco quality improvement intervention of subsequent patient tobacco product use: A national dental PBRN study

ABSTRACT: BACKGROUND: Brief clinician delivered advice helps in tobacco cessation efforts. This study assessed the impact of our intervention on instances of advice given to dental patients during visits on tobacco use quit rates 6 months after the intervention. METHODS: The intervention was cluster randomized trial at the dental practice level. Intervention dental practices were provided a longitudinal technology-assisted intervention, oralcancerprevention.org that included a series of interactive educational cases and motivational email cues to remind dental provides to complete guideline-concordant brief behavioral counseling at the point of care. In all dental practices, exit cards were given to the first 100 consecutive patients, in which tobacco users provided contact information for a six month follow-up telephone survey. RESULTS: A total of 564 tobacco using dental patients completed a six month follow-up survey. Among intervention patients, 55% reported receiving advice to quit tobacco, and 39% of control practice patients reported receiving advice to quit tobacco (p \u3c 0.01). Six-month tobacco use quit rates were not significantly between the Intervention (9%) and Control (13%) groups, (p = 0.088). CONCLUSION: Although we increased rates of cessation advice delivered in dental practices, this study shows no evidence that brief advice by dentist\u27s increases long-term abstinence in smokers.Trial registration: ClinicalTrials.gov NCT00627185

Behavioral states may be associated with distinct spatial patterns in electrocorticogram

To determine if behavioral states are associated with unique spatial electrocorticographic (ECoG) patterns, we obtained recordings with a microgrid electrode array applied to the cortical surface of a human subject. The array was constructed with the intent of extracting maximal spatial information by optimizing interelectrode distances. A 34-year-old patient with intractable epilepsy underwent intracranial ECoG monitoring after standard methods failed to reveal localization of seizures. During the 8-day period of invasive recording, in addition to standard clinical electrodes a square 1 × 1 cm microgrid array with 64 electrodes (1.25 mm separation) was placed on the right inferior temporal gyrus. Careful review of video recordings identified four extended naturalistic behaviors: reading, conversing on the telephone, looking at photographs, and face-to-face interactions. ECoG activity recorded with the microgrid that corresponded to these behaviors was collected and ECoG spatial patterns were analyzed. During periods of ECoG selected for analysis, no electrographic seizures or epileptiform patterns were present. Moments of maximal spatial variance are shown to cluster by behavior. Comparisons between conditions using a permutation test reveal significantly different spatial patterns for each behavior. We conclude that ECoG recordings obtained on the cortical surface with optimal high spatial frequency resolution reveal distinct local spatial patterns that reflect different behavioral states, and we predict that similar patterns will be found in many if not most cortical areas on which a microgrid is placed

Social and contextual influences on antibiotic prescribing and antimicrobial stewardship: a qualitative study with clinical commissioning group and general practice professionals

Antibiotic prescribing in England varies considerably between Clinical Commissioning Groups (CCGs) and general practices. We aimed to assess social and contextual factors affecting antibiotic prescribing and engagement with antimicrobial stewardship (AMS) initiatives. Semi-structured telephone interviews were conducted with 22 CCG professionals and 19 general practice professionals. Interviews were audio-recorded, transcribed, and analyzed thematically. Social/contextual influences were grouped into the following four categories: (1) Immediate context, i.e., patients’ social characteristics (e.g., deprivation and culture), clinical factors, and practice and clinician characteristics (e.g., “struggling” with staff shortage/turnover) were linked to higher prescribing. (2) Wider context, i.e., pressures on the healthcare system, limited resources, and competing priorities were seen to reduce engagement with AMS. (3) Collaborative and whole system approaches, i.e., communication, multidisciplinary networks, leadership, and teamwork facilitated prioritizing AMS, learning, and consistency. (4) Relativity of appropriate prescribing, i.e., “high” or “appropriate” prescribing was perceived as relative, depending on comparators, and disregarding different contexts, but social norms around antibiotic use among professionals and patients seemed to be changing. Further optimization of antibiotic prescribing would benefit from addressing social/contextual factors and addressing wider health inequalities, not only targeting individual clinicians. Tailoring and adapting to local contexts and constraints, ensuring adequate time and resources for AMS, and collaborative, whole system approaches to promote consistency may help promote AMS

CD44 Upregulation in E-Cadherin-Negative Esophageal Cancers Results in Cell Invasion

E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform. Using an organotypic reconstruct model, we show increased CD44 expression in areas of cell invasion is associated with MMP-9 at the leading edge. Moreover, Activin A increases cell invasion through CD44 upregulation after E-cadherin loss. Taken together, our results provide functional evidence of CD44 upregulation in esophageal cancer invasion

Patient preferences for the allocation of deceased donor kidneys for transplantation: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Deceased donor kidneys are a scarce health resource, yet patient preferences for organ allocation are largely unknown. The aim of this study was to determine patient preferences for how kidneys should be allocated for transplantation.</p> <p>Methods</p> <p>Patients on dialysis and kidney transplant recipients were purposively selected from two centres in Australia to participate in nominal/focus groups in March 2011. Participants identified and ranked criteria they considered important for deceased donor kidney allocation. Transcripts were thematically analysed to identify reasons for their rankings.</p> <p>Results</p> <p>From six groups involving 37 participants, 23 criteria emerged. Most agreed that matching, wait-list time, medical urgency, likelihood of surviving surgery, age, comorbidities, duration of illness, quality of life, number of organs needed and impact on the recipient's life circumstances were important considerations. Underpinning their rankings were four main themes: enhancing life, medical priority, recipient valuation, and deservingness. These were predominantly expressed as achieving equity for all patients, or priority for specific sub-groups of potential recipients regarded as more "deserving".</p> <p>Conclusions</p> <p>Patients believed any wait-listed individual who would gain life expectancy and quality of life compared with dialysis should have access to transplantation. Equity of access to transplantation for all patients and justice for those who would look after their transplant were considered important. A utilitarian rationale based on maximizing health gains from the allocation of a scarce resource to avoid "wastage," were rarely expressed. Organ allocation organisations need to seek input from patients who can articulate preferences for allocation and advocate for equity and justice in organ allocation.</p