Reading policies for joins: An asymptotic analysis

Suppose that $m_n$ observations are made from the distribution $\mathbf {R}$ and $n-m_n$ from the distribution $\mathbf {S}$. Associate with each pair, $x$ from $\mathbf {R}$ and $y$ from $\mathbf {S}$, a nonnegative score $\phi(x,y)$. An optimal reading policy is one that yields a sequence $m_n$ that maximizes $\mathbb{E}(M(n))$, the expected sum of the $(n-m_n)m_n$ observed scores, uniformly in $n$. The alternating policy, which switches between the two sources, is the optimal nonadaptive policy. In contrast, the greedy policy, which chooses its source to maximize the expected gain on the next step, is shown to be the optimal policy. Asymptotics are provided for the case where the $\mathbf {R}$ and $\mathbf {S}$ distributions are discrete and $\phi(x,y)=1 or 0$ according as $x=y$ or not (i.e., the observations match). Specifically, an invariance result is proved which guarantees that for a wide class of policies, including the alternating and the greedy, the variable M(n) obeys the same CLT and LIL. A more delicate analysis of the sequence $\mathbb{E}(M(n))$ and the sample paths of M(n), for both alternating and greedy, reveals the slender sense in which the latter policy is asymptotically superior to the former, as well as a sense of equivalence of the two and robustness of the former.Comment: Published at http://dx.doi.org/10.1214/105051606000000646 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

The BARISTA: A model for bid arrivals in online auctions

The arrival process of bidders and bids in online auctions is important for studying and modeling supply and demand in the online marketplace. A popular assumption in the online auction literature is that a Poisson bidder arrival process is a reasonable approximation. This approximation underlies theoretical derivations, statistical models and simulations used in field studies. However, when it comes to the bid arrivals, empirical research has shown that the process is far from Poisson, with early bidding and last-moment bids taking place. An additional feature that has been reported by various authors is an apparent self-similarity in the bid arrival process. Despite the wide evidence for the changing bidding intensities and the self-similarity, there has been no rigorous attempt at developing a model that adequately approximates bid arrivals and accounts for these features. The goal of this paper is to introduce a family of distributions that well-approximate the bid time distribution in hard-close auctions. We call this the BARISTA process (Bid ARrivals In STAges) because of its ability to generate different intensities at different stages. We describe the properties of this model, show how to simulate bid arrivals from it, and how to use it for estimation and inference. We illustrate its power and usefulness by fitting simulated and real data from eBay.com. Finally, we show how a Poisson bidder arrival process relates to a BARISTA bid arrival process.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS117 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring.  Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice

The Disconnect Between the Guidelines, the Appropriate Use Criteria, and Reimbursement Coverage Decisions The Ultimate Dilemma

Recently, the American College of Cardiology Foundation in collaboration with the Heart Rhythm Society published appropriate use criteria (AUC) for implantable cardioverter-defibrillators and cardiac resynchronization therapy. These criteria were developed to critically review clinical situations that may warrant implantation of an implantable cardioverter-defibrillator or cardiac resynchronization therapy device, and were based on a synthesis of practice guidelines and practical experience from a diverse group of clinicians. When the AUC was drafted, the writing committee recognized that some of the scenarios that were deemed “appropriate” or “may be appropriate” were discordant with the clinical requirements of many payers, including the Medicare National Coverage Determination (NCD). To charge Medicare for a procedure that is not covered by the NCD may be construed as fraud. Discordance between the guidelines, the AUC, and the NCD places clinicians in the difficult dilemma of trying to do the “right thing” for their patients, while recognizing that the “right thing” may not be covered by the payer or insurer. This commentary addresses these issues. Options for reconciling this disconnect are discussed, and recommendations to help clinicians provide the best care for their patients are offered

Collagenase clostridium histolyticum for the treatment of Peyronie's disease: a prospective Italian multicentric study

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0–40)° or 42.9 (0–67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three-injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment

Monomeric and Dimeric CXCL8 Are Both Essential for In Vivo Neutrophil Recruitment

Rapid mobilization of neutrophils from vasculature to the site of bacterial/viral infections and tissue injury is a critical step in successful resolution of inflammation. The chemokine CXCL8 plays a central role in recruiting neutrophils. A characteristic feature of CXCL8 is its ability to reversibly exist as both monomers and dimers, but whether both forms exist in vivo, and if so, the relevance of each form for in vivo function is not known. In this study, using a ‘trapped’ non-associating monomer and a non-dissociating dimer, we show that (i) wild type (WT) CXCL8 exists as both monomers and dimers, (ii) the in vivo recruitment profiles of the monomer, dimer, and WT are distinctly different, and (iii) the dimer is essential for initial robust recruitment and the WT is most active for sustained recruitment. Using a microfluidic device, we also observe that recruitment is not only dependent on the total amount of CXCL8 but also on the steepness of the gradient, and the gradients created by different CXCL8 variants elicit different neutrophil migratory responses. CXCL8 mediates its function by binding to CXCR2 receptor on neutrophils and glycosaminoglycans (GAGs) on endothelial cells. On the basis of our data, we propose that dynamic equilibrium between CXCL8 monomers and dimers and their differential binding to CXCR2 and GAGs mediates and regulates in vivo neutrophil recruitment. Our finding that both CXCL8 monomer and dimer are functional in vivo is novel, and indicates that the CXCL8 monomer-dimer equilibrium and neutrophil recruitment are intimately linked in health and disease

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570