Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predomi- nantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase ‘paradigm shift’ in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and col- leagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the man- agement of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples’ dogma makes his contribution truly a genuine paradigm shift

Opioid use among low back pain patients in primary care: Is opioid prescription associated with disability at 6-month follow-up?

Opioid prescribing for chronic noncancer pain is increasing, but there is limited knowledge about longer-term outcomes of people receiving opioids for conditions such as back pain. This study aimed to explore the relationship between prescribed opioids and disability among patients consulting in primary care with back pain. A total of 715 participants from a prospective cohort study, who gave consent for review of medical and prescribing records and completed baseline and 6month follow-up questionnaires, were included. Opioid prescription data were obtained from electronic prescribing records, and morphine equivalent doses were calculated. The primary outcome was disability (Roland-Morris Disability Questionnaire [RMDQ]) at 6months. Multivariable linear regression was used to examine the association between opioid prescription at baseline and RMDQ score at 6months. Analyses were adjusted for potential confounders using propensity scores reflecting the probability of opioid prescription given baseline characteristics. In the baseline period, 234 participants (32.7%) were prescribed opioids. In the final multivariable analysis, opioid prescription at baseline was significantly associated with higher disability at 6-month follow-up (P<.022), but the magnitude of this effect was small, with a mean RMDQ score of 1.18 (95% confidence interval: 0.17 to 2.19) points higher among those prescribed opioids compared to those who were not. Our findings indicate that even after adjusting for a substantial number of potential confounders, opioids were associated with slightly worse functioning in back pain patients at 6-month follow-up. Further research may help us to understand the mechanisms underlying these findings and inform clinical decisions regarding the usefulness of opioids for back pain

Enhanced antipneumococcal antibody electrochemiluminescence assay: validation and bridging to the WHO reference ELISA

AIM: To re-optimize the pneumococcal (Pn) electrochemiluminescence (ECL) assay and to validate and bridge the enhanced assay to the WHO ELISA, to support the Phase III clinical trial program for V114, a 15-valent Pn conjugate vaccine. MATERIALS & METHODS: The Pn ECL assay was re-optimized, validated and formally bridged to the WHO ELISA. RESULTS: The enhanced Pn ECL assay met all prespecified validation acceptance criteria and demonstrated concordance with the WHO ELISA. The corresponding threshold value remains at 0.35 μg/ml for all 15 serotypes. CONCLUSION: The enhanced Pn ECL assay has been validated for the measurement of antibodies to 15 Pn capsular polysaccharides and is concordant with the WHO ELISA, supporting its use in clinical trials

Anomalous Dimensions and Non-Gaussianity

We analyze the signatures of inflationary models that are coupled to strongly interacting field theories, a basic class of multifield models also motivated by their role in providing dynamically small scales. Near the squeezed limit of the bispectrum, we find a simple scaling behavior determined by operator dimensions, which are constrained by the appropriate unitarity bounds. Specifically, we analyze two simple and calculable classes of examples: conformal field theories (CFTs), and large-N CFTs deformed by relevant time-dependent double-trace operators. Together these two classes of examples exhibit a wide range of scalings and shapes of the bispectrum, including nearly equilateral, orthogonal and local non-Gaussianity in different regimes. Along the way, we compare and contrast the shape and amplitude with previous results on weakly coupled fields coupled to inflation. This signature provides a precision test for strongly coupled sectors coupled to inflation via irrelevant operators suppressed by a high mass scale up to 1000 times the inflationary Hubble scale.Comment: 40 pages, 10 figure

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Dimensionality and dynamics in the behavior of C. elegans

A major challenge in analyzing animal behavior is to discover some underlying simplicity in complex motor actions. Here we show that the space of shapes adopted by the nematode C. elegans is surprisingly low dimensional, with just four dimensions accounting for 95% of the shape variance, and we partially reconstruct "equations of motion" for the dynamics in this space. These dynamics have multiple attractors, and we find that the worm visits these in a rapid and almost completely deterministic response to weak thermal stimuli. Stimulus-dependent correlations among the different modes suggest that one can generate more reliable behaviors by synchronizing stimuli to the state of the worm in shape space. We confirm this prediction, effectively "steering" the worm in real time.Comment: 9 pages, 6 figures, minor correction

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

&lt;b&gt;Background&lt;/b&gt; High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to &#60;6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of &#60;5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

The Effective Field Theory of Multifield Inflation

We generalize the Effective Field Theory of Inflation to include additional light scalar degrees of freedom that are in their vacuum at the time the modes of interest are crossing the horizon. In order to make the scalars light in a natural way we consider the case where they are the Goldstone bosons of a global symmetry group or are partially protected by an approximate supersymmetry. We write the most general Lagrangian that couples the scalar mode associated to the breaking of time translation during inflation to the additional light scalar fields. This Lagrangian is constrained by diffeomorphism invariance and the additional symmetries that keep the new scalars light. This Lagrangian describes the fluctuations around the time of horizon crossing and it is supplemented with a general parameterization describing how the additional fluctuating fields can affect cosmological perturbations. We find that multifield inflation can reproduce the non-Gaussianities that can be generated in single field inflation but can also give rise to new kinds of non-Gaussianities. We find several new three-point function shapes. We show that in multifield inflation it is possible to naturally suppress the three-point function making the four-point function the leading source of detectable non-Gaussianities. We find that under certain circumstances, i.e. if specific shapes of non-Gaussianities are detected in the data, one could distinguish between single and multifield inflation and sometimes even among the various mechanisms that kept the additional fields light.Comment: 62 pages, 1 figure; v2: JHEP published version, minor corrections, comments and references adde