Sentinel node staging for breast cancer: Intraoperative molecular pathology overcomes conventional histologic sampling errors

BACKGROUND: When sentinel node dissection reveals breast cancer metastasis, completion axillary lymph node dissection is ideally performed during the same operation. Intraoperative histologic techniques have low and variable sensitivity. A new intraoperative molecular assay (GeneSearch BLN Assay; Veridex, LLC, Warren, NJ) was evaluated to determine its efficiency in identifying significant sentinel lymph node metastases (\u3e.2 mm). METHODS: Positive or negative BLN Assay results generated from fresh 2-mm node slabs were compared with results from conventional histologic evaluation of adjacent fixed tissue slabs. RESULTS: In a prospective study of 416 patients at 11 clinical sites, the assay detected 98% of metastases \u3e2 mm and 88% of metastasis greater \u3e.2 mm, results superior to frozen section. Micrometastases were less frequently detected (57%) and assay positive results in nodes found negative by histology were rare (4%). CONCLUSIONS: The BLN Assay is properly calibrated for use as a stand alone intraoperative molecular test

Cryoablation of Early-Stage Breast Cancer: Work-in-Progress Report of a Multi-Institutional Trial

With recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41403/1/10434_2004_Article_542.pd

A Trait‐Based Framework for Assessing the Vulnerability of Marine Species to Human Impacts

Marine species and ecosystems are widely affected by anthropogenic stressors, ranging from pollution and fishing to climate change. Comprehensive assessments of how species and ecosystems are impacted by anthropogenic stressors are critical for guiding conservation and management investments. Previous global risk or vulnerability assessments have focused on marine habitats, or on limited taxa or specific regions. However, information about the susceptibility of marine species across a range of taxa to different stressors everywhere is required to predict how marine biodiversity will respond to human pressures. We present a novel framework that uses life-history traits to assess species’ vulnerability to a stressor, which we compare across more than 44,000 species from 12 taxonomic groups (classes). Using expert elicitation and literature review, we assessed every combination of each of 42 traits and 22 anthropogenic stressors to calculate each species’ or representative species group’s sensitivity and adaptive capacity to stressors, and then used these assessments to derive their overall relative vulnerability. The stressors with the greatest potential impact were related to biomass removal (e.g., fisheries), pollution, and climate change. The taxa with the highest vulnerabilities across the range of stressors were mollusks, corals, and echinoderms, while elasmobranchs had the highest vulnerability to fishing-related stressors. Traits likely to confer vulnerability to climate change stressors were related to the presence of calcium carbonate structures, and whether a species exists across the interface of marine, terrestrial, and atmospheric realms. Traits likely to confer vulnerability to pollution stressors were related to planktonic state, organism size, and respiration. Such a replicable, broadly applicable method is useful for informing ocean conservation and management decisions at a range of scales, and the framework is amenable to further testing and improvement. Our framework for assessing the vulnerability of marine species is the first critical step toward generating cumulative human impact maps based on comprehensive assessments of species, rather than habitats

Self-reported ill health in male UK Gulf War veterans: a retrospective cohort study

BACKGROUND: Forces deployed to the first Gulf War report more ill health than veterans who did not serve there. Many studies of post-Gulf morbidity are based on relatively small sample sizes and selection bias is often a concern. In a setting where selection bias relating to the ill health of veterans may be reduced, we: i) examined self-reported adult ill health in a large sample of male UK Gulf War veterans and a demographically similar non-deployed comparison group; and ii) explored self-reported ill health among veterans who believed that they had Gulf War syndrome. METHODS: This study uses data from a retrospective cohort study of reproduction and child health in which a validated postal questionnaire was sent to all UK Gulf War veterans (GWV) and a comparison cohort of Armed Service personnel who were not deployed to the Gulf (NGWV). The cohort for analysis comprises 42,818 males who responded to the questionnaire. RESULTS: We confirmed that GWV report higher rates of general ill health. GWV were significantly more likely to have reported at least one new medical symptom or disease since 1990 than NGWV (61% versus 37%, OR 2.7, 95% CI 2.5–2.8). They were also more likely to report higher numbers of symptoms. The strongest associations were for mood swings (OR 20.9, 95%CI 16.2–27.0), memory loss/lack of concentration (OR 19.6, 95% CI 15.5–24.8), night sweats (OR 9.9, 95% CI 6.5–15.2), general fatigue (OR 9.6, 95% CI 8.3–11.1) and sexual dysfunction (OR 4.6, 95%CI 3.2–6.6). 6% of GWV believed they had Gulf War syndrome (GWS), and this was associated with the highest symptom reporting. CONCLUSIONS: Increased levels of reported ill health among GWV were confirmed. This study was the first to use a questionnaire which did not focus specifically on the veterans' symptoms themselves. Nevertheless, the results are consistent with those of other studies of post-Gulf war illness and thus strengthen overall findings in this area of research. Further examination of the mechanisms underlying the reporting of ill health is required

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013–March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56–7.50]); risk group (OR, 5.65 [95% CI, 3.27–9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64–4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07–3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10–3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31–.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups