Utilization of direct smears of thyroid fine‐needle aspirates for ancillary molecular testing: A comparison of two proprietary testing platforms

Background Ancillary molecular testing has been recommended for thyroid fine‐needle aspirates (FNA) with indeterminate cytologic diagnoses. Rosetta Genomics and Interpace Diagnostics have developed assays that can utilize direct smears as the testing substrate. Methods A retrospective study of indeterminate thyroid FNAs with known histologic follow‐up was performed. One Diff‐Quik‐stained smear and one Papanicolaou‐stained smear with similar cellularity (at least 60‐100 lesional cells) from each case were sent to Rosetta and Interpace, respectively, for analysis. The results were directly compared and correlated with the final histopathology. Neither company was aware of the follow‐up histologic findings in these cases. Results A total of 10 thyroid FNAs were identified from our 2015 files. The cytologic diagnoses included follicular lesion of undetermined significance (FLUS, n = 5), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN, n = 4), and suspicious for malignancy (SM, n = 1). Of the seven cases with benign histology, six smears were classified as benign by the RosettaGX microRNA classifier, and one case was designated as suspicious. Five cases were negative by both ThyGenX oncogene panel and ThyraMIR microRNA classifier. One case was negative by ThyGenX and positive on follow‐up ThyraMIR, and one case was positive for KRAS mutation and positive on ThyraMIR. Both the RosettaGX and ThyGenX/ThyraMIR tests demonstrated positive results for the three histologically malignant cases. Conclusion This study demonstrates that two molecular testing platforms performed equally well using our stained direct smears. Both molecular tests revealed a 100% negative predictive rate. RosettaGX showed a 75% positive predictive value in comparison to 60% for ThyGenX/ThyraMIR

Tributes to Professor Alan Hornstein

Tributes to Professor Alan Hornstein upon his retirement from the University of Maryland School of Law

The Role of NF-κB in PPARα-Mediated Hepatocarcinogenesis

In this review, the role of NF-κB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-κB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-α (PPARα) activation in non-hepatic tissues can lead to the inhibition of NF-κB activation. Several lines of evidence support the hypothesis that the activation of NF-κB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-κB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-κB knockout models. Specifically, the induction of cell proliferation and the promotion of liver carcinogenesis are inhibited in mice lacking the p50 subunit of NF-κB. Overall, the activation of NF-κB appears to be important in the carcinogenic activity of peroxisome proliferators

Junior doctors’ communication with hospital pharmacists about prescribing: findings from a qualitative interview study

Objectives To explore factors affecting communication between Foundation Year (FY) 1 doctors and hospital pharmacists about prescribing from the junior doctors’ perspective. Methods Trained interviewers (n=4) conducted semistructured interviews with FY1 doctors who were purposively sampled from three hospitals in England. FY1 doctors were asked about their experiences of communication with hospital pharmacists about their prescribing; instances where they disagreed with or did not implement a hospital pharmacist’s recommendation; and their preferences for communicating with hospital pharmacists about prescribing. Interviews were audiorecorded, transcribed verbatim and analysed thematically. Results A total of 27 FY1 doctors were interviewed. Findings were categorised into four main themes: (1) nature and context of communication; (2) FY1 doctors’ perceptions of communication with hospital pharmacists; (3) factors influencing FY1 doctors’ decision whether to act on pharmacists’ prescribing recommendations; and (4) suggestions to improve communication with pharmacists. FY1 doctors and hospital pharmacists generally communicated well. FY1 doctors appreciated and frequently acted on pharmacists’ advice yet there was deference to senior medical staff when advice differed. Joint ward rounds, pharmacist-led teaching sessions and a standardised approach to communication were all suggested as ways to improve communication and may increase the likelihood of pharmacists’ recommendations being acted on. Conclusions FY1 doctors and hospital pharmacists communicated frequently about medication prescribing. Issues occurred when there were differences in professional judgement between senior medical staff and pharmacists but these were usually resolved satisfactorily for the FY1 doctor. Further interventions to improve communication and safe prescribing could involve a multidisciplinary and systems approach

Drama-based education to motivate participation in substance abuse prevention

BACKGROUND: The substance abuse prevention goal of the theatre production "TUNNELS" was to provide community education on substance abuse to an audience in Durham, NC and surrounding communities. The education effort intended to increase awareness and understanding of the risk and protective factors associated with alcohol and other drug use, and to promote pro-active behaviors in substance abuse prevention within the adult community. It was hypothesized that community-based education via drama would change attitudes toward alcohol and substance abuse, and increase participation in family and community activities aimed at substance abuse prevention. METHODS: A focus group comprised of educators, substance abuse researchers and local substance abuse counselors developed "life stories" of users of alcohol and other drugs and a local playwright incorporated these and other experiences into a series of six vignettes. The production was publicized throughout the Durham area, and 700 adults attending the play signed a consent form and completed the pre-play survey. The participant pool was restricted to those adults who completed both the time-1 and time-2 surveys and resided within Durham and surrounding communities. Paired comparisons of mean responses were analyzed using a paired sample two-tailed t-test. A telephone survey three months after the play assessed attitudes toward substance abuse as a disease, and whether the respondents had increased their participation in prevention activities including discussions of the play with others. RESULTS: Viewing the play increased the knowledge base of participants regarding substance abuse as a disease, even though the audience demonstrated an appreciation of risk and protective factors prior to attending the performance. In the pre-play survey, participants indicated a strong opinion that parental involvement in teen life was important, and therefore this was not increased as a result of viewing the play. It was found that the drama increased intent to participate in substance abuse prevention activities at home and in the community. Follow-up surveys performed three months after the performance indicated that participants had discussed the play with others and had increased their participation in substance abuse prevention activities, particularly regarding donations of money. CONCLUSION: Drama incorporates a component of emotional response to the informational content, and the combination of emotion and information works together to promote individual intentions to become more involved in family and community prevention activities. This study demonstrates the efficacy of drama as a mechanism to educate and motivate. Support for this mechanism is warranted at the level of state, local community, school district, and faith-based and community organizations

True durability: HIV virologic suppression in an urban clinic and implications for timing of intensive adherence efforts and viral load monitoring.

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound \u3eLLOQ from the first viral load was 36.9 % (95 % CI 32.2-41.6) in the first year, 26.9 % (95 % CI 21.7-32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI 18.4-30.9) in the year following 2 years of viral suppression. However, for patients with CD4 ≥300 cells/µl who had 3-6 years of virologic suppression, the risk of viral rebound was very low. At the population level, the risk of viral rebound in a complex urban clinic population is surprisingly high even out to 3 years. Intensified monitoring and adherence efforts should target this high risk period. Thereafter, confidence in truly durable virologic suppression is improved

True durability: HIV virologic suppression in an urban clinic and implications for timing of intensive adherence efforts and viral load monitoring

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound \u3eLLOQ from the first viral load was 36.9 % (95 % CI 32.2–41.6) in the first year, 26.9 % (95 % CI 21.7–32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI 18.4–30.9) in the year following 2 years of viral suppression. However, for patients with CD4 ≥300 cells/µl who had 3–6 years of virologic suppression, the risk of viral rebound was very low. At the population level, the risk of viral rebound in a complex urban clinic population is surprisingly high even out to 3 years. Intensified monitoring and adherence efforts should target this high risk period. Thereafter, confidence in truly durable virologic suppression is improved

Recommendations for Medical Management of Adult Lead Exposure

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 μg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 μg/dL or if two successive blood lead concentrations measured over a 4-week interval are ≥ 20 μg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 μg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 μg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 μg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 μg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations

KELT-11b: A Highly Inflated Sub-Saturn Exoplanet Transiting the V=8 Subgiant HD 93396

We report the discovery of a transiting exoplanet, KELT-11b, orbiting the bright ($V=8.0$) subgiant HD 93396. A global analysis of the system shows that the host star is an evolved subgiant star with $T_{\rm eff} = 5370\pm51$ K, $M_{*} = 1.438_{-0.052}^{+0.061} M_{\odot}$, $R_{*} = 2.72_{-0.17}^{+0.21} R_{\odot}$, log $g_*= 3.727_{-0.046}^{+0.040}$, and [Fe/H]$= 0.180\pm0.075$. The planet is a low-mass gas giant in a $P = 4.736529\pm0.00006$ day orbit, with $M_{P} = 0.195\pm0.018 M_J$, $R_{P}= 1.37_{-0.12}^{+0.15} R_J$, $\rho_{P} = 0.093_{-0.024}^{+0.028}$ g cm$^{-3}$, surface gravity log ${g_{P}} = 2.407_{-0.086}^{+0.080}$, and equilibrium temperature $T_{eq} = 1712_{-46}^{+51}$ K. KELT-11 is the brightest known transiting exoplanet host in the southern hemisphere by more than a magnitude, and is the 6th brightest transit host to date. The planet is one of the most inflated planets known, with an exceptionally large atmospheric scale height (2763 km), and an associated size of the expected atmospheric transmission signal of 5.6%. These attributes make the KELT-11 system a valuable target for follow-up and atmospheric characterization, and it promises to become one of the benchmark systems for the study of inflated exoplanets.Comment: 15 pages, Submitted to AAS Journal